Screening method and compounds for modulating telomerase activity

Abstract

The present invention embraces methods for identifying compounds that modulate the activity of telomerase. Compounds of the invention are identified by designing or screening for a compound which binds to at least one amino acid residue of the TRBD, “thumb,” “finger,” and/or “palm” domain; or FP-pocket, PT-pocket or Th-pocket of telomerase and testing the compound for its ability to modulate the activity of telomerase. Compounds selected for interacting with the T-pocket or Fingers-Palm pocket of telomerase are also provided.

What is claimed is:  
     
       1. A pharmaceutical composition comprising a compound having a structure of Formula IV in admixture with a pharmaceutically acceptable carrier, 
       
         
           
           
               
               
           
         
       
       wherein
 R 9  and the dashed bond are either present or absent, wherein when R 9  is present R 9  is oxygen or carbon; 
 R 10  and R 11  are independently hydrogen or a carboxyl group; 
 R 12  and R 13  are independently —C(O)NH— or —NHC(O)—; and 
 R 14  and R 15  are independently an unsubstituted heterocyclic group or a benzene or heterocyclic group substituted with at least one substituent comprising a lower alkyl, amine, oxo, or —OC(O)CH 3 . 
 
     
     
       2. The pharmaceutical composition of  claim 1 , further comprising a cancer therapeutic agent. 
     
     
       3. The pharmaceutical composition of  claim 2 , wherein the cancer therapeutic agent comprises a chemotherapeutic agent or radiotherapeutic agent.